Research in my laboratory is centered on the study of cell proliferation and cell transformation. The control of gene expression in quiescent primary chicken embryo fibroblasts (CEF) is the focus of our current research program. In particular, we recently uncovered a novel response to the conditions of limited oxygen concentrations experienced by contact inhibited CEF and showed that this response is critical for the maintenance of lipid/membrane homeostasis and cell survival. Current investigations have for objective to characterize the cellular processes regulated by the lipid/membrane damage response promoting reversible growth arrest and survival of quiescent cells. To do this work we employ basic techniques of cell and molecular biology as well as genomic, proteomic and lipidomic approaches.

Research in my laboratory is centered on the study of cell proliferation and cell transformation. The control of gene expression in quiescent primary chicken embryo fibroblasts (CEF) is the focus of our current research program. In particular, we recently uncovered a novel response to the conditions of limited oxygen concentrations experienced by contact inhibited CEF and showed that this response is critical for the maintenance of lipid/membrane homeostasis and cell survival. Current investigations have for objective to characterize the cellular processes regulated by the lipid/membrane damage response promoting reversible growth arrest and survival of quiescent cells. To do this work we employ basic techniques of cell and molecular biology as well as genomic, proteomic and lipidomic approaches.

Plants like animals defend themselves from disease and sometimes succumb to microbial disease. My research group is interested in understanding the molecular genetic and biochemical mechanisms of plant immunity. Our long-term goal is to translate our plant immunity knowledge to reduce crop loss and pesticide use in agriculture. After many years of challenging research, my team demonstrated that DIR1 proteins move via the phloem from an initially infected leaf to distant leaves to participate in alerting/priming distant leaves to respond in a resistant manner to future microbial infections. Knowing that DIR1 is a key protein involved in inter-organ communication to initiate resistance, will allow us to dissect the priming response in distant leaves. We are using this knowledge to find environmentally friendly chemical treatments that initiate natural plant defense to provide pesticide-free methods to protect Ontario greenhouse-grown cucumbers and tomatoes from disease. We also study the Age-Related Resistance response in which plants become highly resistant to normally virulent pathogens as they mature. What molecular changes allow a mature plant to perceive and effectively defend against normally virulent pathogens, is another fascinating question we are investigating. As an instructor my goals include convincing students/future citizens that contrary to popular opinion, plants are fascinating and incredibly important for people and the planet. As a mentor to undergraduate and graduate students, I facilitate their growth as scientists and people. I encourage them to improve in areas they find challenging by reminding them it takes time, but it’s worth it.

Plants like animals defend themselves from disease and sometimes succumb to microbial disease. My research group is interested in understanding the molecular genetic and biochemical mechanisms of plant immunity. Our long-term goal is to translate our plant immunity knowledge to reduce crop loss and pesticide use in agriculture. After many years of challenging research, my team demonstrated that DIR1 proteins move via the phloem from an initially infected leaf to distant leaves to participate in alerting/priming distant leaves to respond in a resistant manner to future microbial infections. Knowing that DIR1 is a key protein involved in inter-organ communication to initiate resistance, will allow us to dissect the priming response in distant leaves. We are using this knowledge to find environmentally friendly chemical treatments that initiate natural plant defense to provide pesticide-free methods to protect Ontario greenhouse-grown cucumbers and tomatoes from disease. We also study the Age-Related Resistance response in which plants become highly resistant to normally virulent pathogens as they mature. What molecular changes allow a mature plant to perceive and effectively defend against normally virulent pathogens, is another fascinating question we are investigating. As an instructor my goals include convincing students/future citizens that contrary to popular opinion, plants are fascinating and incredibly important for people and the planet. As a mentor to undergraduate and graduate students, I facilitate their growth as scientists and people. I encourage them to improve in areas they find challenging by reminding them it takes time, but it’s worth it.

Cancer Biology, Cadherin-Catenin mediated Cell adhesion and Signaling, POZ Transcription Factors Our research goal is to understand the cellular and molecular basis of E-cadherin-mediated adhesion in normal cell growth, development and tumourigenesis. The primary epithelial cell-cell adhesion system involving E-cadherin and its catenin cofactors a-, b-, g- and p120ctn, is perturbed in ~50% of human metastatic tumours, and this correlates with the invasive phenotype. Interestingly, the catenins also function as transcriptional regulators of genes involved in tumourigenesis. My laboratory focuses on the transcription factor Kaiso that was first identified as a specific binding partner for the catenin p120ctn, which is aberrantly expressed or absent in human breast, colon and skin carcinomas. Kaiso is a novel member of the POZ-zinc finger family of transcription factors implicated as oncoproteins or tumor suppressors, and currently it is the only known POZ protein with bi-modal DNA-binding and transcriptional repression activity; Kaiso recognizes a sequence-specific consensus, TCCTGCNA, or methylated CpG-dinucleotides.

Cancer Biology, Cadherin-Catenin mediated Cell adhesion and Signaling, POZ Transcription Factors Our research goal is to understand the cellular and molecular basis of E-cadherin-mediated adhesion in normal cell growth, development and tumourigenesis. The primary epithelial cell-cell adhesion system involving E-cadherin and its catenin cofactors a-, b-, g- and p120ctn, is perturbed in ~50% of human metastatic tumours, and this correlates with the invasive phenotype. Interestingly, the catenins also function as transcriptional regulators of genes involved in tumourigenesis. My laboratory focuses on the transcription factor Kaiso that was first identified as a specific binding partner for the catenin p120ctn, which is aberrantly expressed or absent in human breast, colon and skin carcinomas. Kaiso is a novel member of the POZ-zinc finger family of transcription factors implicated as oncoproteins or tumor suppressors, and currently it is the only known POZ protein with bi-modal DNA-binding and transcriptional repression activity; Kaiso recognizes a sequence-specific consensus, TCCTGCNA, or methylated CpG-dinucleotides.

At one level, evolution is remarkably simple, with just a few concepts (mutation, recombination, random drift and natural selection) that underlie the overall process. Yet this description obscures many issues that make evolution a fascinating area for study. Evolution typically involves many genes and often revolves around interactions between individuals and their environments. Moreover, genes interact with one another and with the environment in a nonlinear fashion, resulting in complex phenotypes and evolutionary dynamics. My work aims to describe and analyze such interactions with experimental and quantitative rigor. Specifically work in my lab aims to address the fundamental question about the mechanistic basis of observed phenotypic variation. That is, how genetic (and environmental) variation modulate developmental processes and ultimately influence phenotypic outcomes. My research employs genetic and genomic approaches to address these issues, largely using Drosophila (fruit flies) as a model system. Most labs that work with Drosophila study either individual mutations of large effect (such as those that completely knock out a particular function) or subtle quantitative variation (rarely identifying specific genes). We employ both of these empirical approaches in conjunction with our genomic analyses to help relate our understanding from developmental genetics with the natural variation observed in populations.

At one level, evolution is remarkably simple, with just a few concepts (mutation, recombination, random drift and natural selection) that underlie the overall process. Yet this description obscures many issues that make evolution a fascinating area for study. Evolution typically involves many genes and often revolves around interactions between individuals and their environments. Moreover, genes interact with one another and with the environment in a nonlinear fashion, resulting in complex phenotypes and evolutionary dynamics. My work aims to describe and analyze such interactions with experimental and quantitative rigor. Specifically work in my lab aims to address the fundamental question about the mechanistic basis of observed phenotypic variation. That is, how genetic (and environmental) variation modulate developmental processes and ultimately influence phenotypic outcomes. My research employs genetic and genomic approaches to address these issues, largely using Drosophila (fruit flies) as a model system. Most labs that work with Drosophila study either individual mutations of large effect (such as those that completely knock out a particular function) or subtle quantitative variation (rarely identifying specific genes). We employ both of these empirical approaches in conjunction with our genomic analyses to help relate our understanding from developmental genetics with the natural variation observed in populations.

Development in multicellular bacteria; Regulation by small RNAs; Antibiotic production The goal of our research is to understand development and regulation in multicellular bacteria, using Streptomyces coelicolor as our model system. The streptomycetes are extremely important to the pharmaceutical industry as they make a large number of secondary metabolites having a profound medical benefit, including anti-cancer agents, immunosuppressants, and the majority of clinically useful antibiotics. They are also unusual in that they have a complex, multicellular life cycle and are capable of differentiating into distinct tissue types. Intriguingly, this differentiation process coincides with the production of secondary metabolites. One aspect of our research is focused on understanding the components necessary for differentiation, and centres on a novel family of proteins, termed the chaplins, that are essential for the transition from one differentiated state to another. We are also interested in the regulatory networks that control differentiation, metabolism, and environmental adaptation in S. coelicolor, and are focussing on a newly emerging, and universally important, class of regulators known as the small RNAs.

Development in multicellular bacteria; Regulation by small RNAs; Antibiotic production The goal of our research is to understand development and regulation in multicellular bacteria, using Streptomyces coelicolor as our model system. The streptomycetes are extremely important to the pharmaceutical industry as they make a large number of secondary metabolites having a profound medical benefit, including anti-cancer agents, immunosuppressants, and the majority of clinically useful antibiotics. They are also unusual in that they have a complex, multicellular life cycle and are capable of differentiating into distinct tissue types. Intriguingly, this differentiation process coincides with the production of secondary metabolites. One aspect of our research is focused on understanding the components necessary for differentiation, and centres on a novel family of proteins, termed the chaplins, that are essential for the transition from one differentiated state to another. We are also interested in the regulatory networks that control differentiation, metabolism, and environmental adaptation in S. coelicolor, and are focussing on a newly emerging, and universally important, class of regulators known as the small RNAs.

My group at McMaster University is interested in the area of molecular evolution, bioinformatics, and sequence analysis. Our research attempts to understand how the processes of evolution act to cause the changes observed between molecules, between genes and between genomes. The recent advances in molecular genetics are providing a storm of new data on DNA sequences, on gene structure and higher order genomic structure. However, the implications of these new data are not always clear. This area of scientific inquiry is inter-disciplinary between biology, computer science and mathematics. We make use of computer based analysis, statistical analysis and mathematical models to answer broad questions about the molecular biology of all organisms.

My group at McMaster University is interested in the area of molecular evolution, bioinformatics, and sequence analysis. Our research attempts to understand how the processes of evolution act to cause the changes observed between molecules, between genes and between genomes. The recent advances in molecular genetics are providing a storm of new data on DNA sequences, on gene structure and higher order genomic structure. However, the implications of these new data are not always clear. This area of scientific inquiry is inter-disciplinary between biology, computer science and mathematics. We make use of computer based analysis, statistical analysis and mathematical models to answer broad questions about the molecular biology of all organisms.

Vulval development in Caenorhabditis elegans, Regulation and function of gene networks, Evolution of developmental mechanisms Specification of cell fate during development involves a large number of genes that interact with each other and are expressed in dynamic patterns. My lab is interested in understanding the function and evolution of gene networks that control cell proliferation and differentiation. Alterations in gene regulation have been shown to give rise to severe developmental abnormalities including hereditary diseases and cancers. Hence, a fundamental understanding of gene regulatory networks is critical for gaining important insights into the pathogenesis of human diseases. Toward this goal, we are studying vulva development in an established model organism, Caenorhabditis elegans and a closely related species, Caenorhabditis briggsae. The hermaphrodite vulva provides a unique opportunity to identify genes and study their regulation and function during development. In C. elegans, vulva is formed by the progeny of three out of six multipotential vulval precursor cells (VPCs) that divide three times to give rise to twenty-two cells. The vulval progeny differentiate during L4 larval stage to generate seven different cell types leading to the formation of an adult vulva. The invariant lineage of the VPCs and stereotypic positions of their progeny offer experimental analyses at single-cell resolution.

Vulval development in Caenorhabditis elegans, Regulation and function of gene networks, Evolution of developmental mechanisms Specification of cell fate during development involves a large number of genes that interact with each other and are expressed in dynamic patterns. My lab is interested in understanding the function and evolution of gene networks that control cell proliferation and differentiation. Alterations in gene regulation have been shown to give rise to severe developmental abnormalities including hereditary diseases and cancers. Hence, a fundamental understanding of gene regulatory networks is critical for gaining important insights into the pathogenesis of human diseases. Toward this goal, we are studying vulva development in an established model organism, Caenorhabditis elegans and a closely related species, Caenorhabditis briggsae. The hermaphrodite vulva provides a unique opportunity to identify genes and study their regulation and function during development. In C. elegans, vulva is formed by the progeny of three out of six multipotential vulval precursor cells (VPCs) that divide three times to give rise to twenty-two cells. The vulval progeny differentiate during L4 larval stage to generate seven different cell types leading to the formation of an adult vulva. The invariant lineage of the VPCs and stereotypic positions of their progeny offer experimental analyses at single-cell resolution.

Molecular Genetics ofTay-Sachs disease and Sialidosis. My research focuses on the molecular genetics of two diseases, Tay-Sachs and sialidosis, which are lysosomal storage disorders caused by defects in ?-hexosaminidase A and sialidase respectively. The lysosomal storage process begins in the fetus early in pregnancy but most of these diseases become clinically evident within the first 2 years or have a later onset. The majority of patients show a fatal course with progressive involvement of the nervous system. We have focused on identifying disease-causing mutations in order to determine the impact of these mutations on disease phenotype. This provides informative genotype/phenotype correlations and a precise understanding of the structure/function of the enzymes. With the discovery of more mutant alleles, we have utilized this DNA-based technology to complement the enzyme-based prenatal diagnostic procedures. We are also developing mouse models of Tay-Sachs disease and sialidosis which will allow us to study the pathophysiology of the diseases in order to test potential therapeutic strategies in vivo. Finally, we are developing recombinant adenovirus vectors coding for the human sialidase gene for therapeutic applications. Adenoviral vectors represent a new class of biotherapeutics and its development for gene therapy holds much hope for patients.

Molecular Genetics ofTay-Sachs disease and Sialidosis. My research focuses on the molecular genetics of two diseases, Tay-Sachs and sialidosis, which are lysosomal storage disorders caused by defects in ?-hexosaminidase A and sialidase respectively. The lysosomal storage process begins in the fetus early in pregnancy but most of these diseases become clinically evident within the first 2 years or have a later onset. The majority of patients show a fatal course with progressive involvement of the nervous system. We have focused on identifying disease-causing mutations in order to determine the impact of these mutations on disease phenotype. This provides informative genotype/phenotype correlations and a precise understanding of the structure/function of the enzymes. With the discovery of more mutant alleles, we have utilized this DNA-based technology to complement the enzyme-based prenatal diagnostic procedures. We are also developing mouse models of Tay-Sachs disease and sialidosis which will allow us to study the pathophysiology of the diseases in order to test potential therapeutic strategies in vivo. Finally, we are developing recombinant adenovirus vectors coding for the human sialidase gene for therapeutic applications. Adenoviral vectors represent a new class of biotherapeutics and its development for gene therapy holds much hope for patients.

We study gene regulation and physiological adaptation in E. coli and other bacteria to better understand how bacteria cause disease and persist in the environment. We also have many collaborative projects with biochemists, engineers, industry and government agencies to develop new tools for monitoring water quality and understanding waste treatment processes from a microbiological perspective. We are using new DNA sequencing technology and bioinformatics analysis tools to track microorganisms, characterize composition of complex microbial communities and conduct comprehensive studies of gene expression.

We study gene regulation and physiological adaptation in E. coli and other bacteria to better understand how bacteria cause disease and persist in the environment. We also have many collaborative projects with biochemists, engineers, industry and government agencies to develop new tools for monitoring water quality and understanding waste treatment processes from a microbiological perspective. We are using new DNA sequencing technology and bioinformatics analysis tools to track microorganisms, characterize composition of complex microbial communities and conduct comprehensive studies of gene expression.

Astro-, Computational, Developmental, and Evolutionary biology (with smattering from Ecology and Physiology); Viruses to elephants, including human menopause and especially gastropods, echinoids, and water bears (oh my).

Astro-, Computational, Developmental, and Evolutionary biology (with smattering from Ecology and Physiology); Viruses to elephants, including human menopause and especially gastropods, echinoids, and water bears (oh my).

According to Canadian Cancer Society, cancer is the leading cause of premature death in Canada and an estimated one out of every four Canadians is expected to die from cancer. An underlying hallmark of cancer is genome instability, which can arise from the disruption of telomere maintenance. The Zhu laboratory is interested in elucidating the molecular mechanism by which human cells maintain their telomere integrity. Knowledge gained from these studies is expected to aid in the design of anti-cancer therapeutics and treatment of cancer patients. Currently the Zhu laboratory focuses on two research areas relevant to telomere maintenance and genome integrity: 1. Elucidating the role of post-translational modifications in telomere maintenance. 2. Elucidating the functional interaction between shelterin proteins and accessary factors.

According to Canadian Cancer Society, cancer is the leading cause of premature death in Canada and an estimated one out of every four Canadians is expected to die from cancer. An underlying hallmark of cancer is genome instability, which can arise from the disruption of telomere maintenance. The Zhu laboratory is interested in elucidating the molecular mechanism by which human cells maintain their telomere integrity. Knowledge gained from these studies is expected to aid in the design of anti-cancer therapeutics and treatment of cancer patients. Currently the Zhu laboratory focuses on two research areas relevant to telomere maintenance and genome integrity: 1. Elucidating the role of post-translational modifications in telomere maintenance. 2. Elucidating the functional interaction between shelterin proteins and accessary factors.